Home phototherapy in the United Kingdom.
Explore the source record for details and available documents.
Community Health Nursing↗
Biomedical subjects
R Hume
Publications and source records attributed to R Hume.
Iodine deficiency associated with parenteral nutrition in extreme preterm infants.
Infants are in negative iodine balance on current standard regimens of total parenteral nutrition, with a mean iodine intake of 3 micro g/kg/day (150 ml/kg/day). The recommended enteral intake of iodine for preterm infants is 30 micro g/kg/day. Gastrointestinal absorption of iodine is high, suggesting that parenteral intakes should approach enteral recommendations.
Age Factors↗
An inadequate glycaemic response to glucagon is linked to insulin resistance in preterm infants?
AIMS: To define clinical, metabolic, and hormonal characteristics of preterm infants relative to glucagon responsiveness. METHODS: Two phase study of 78 preterm infants (25-36 weeks gestation) on regular four hourly feeds anticipating discharge home at 36 weeks mean corrected gestation. In phase 1 infants were fasted until hypoglycaemic, or maximally for eight hours. Endocrine and metabolic profiles were obtained at completion. Phase 2 was performed the following day. A feed was omitted and replaced by a bolus dose of intravenous glucagon (100 micro g/kg). Main outcome measures were measurements of blood glucose and lactate concentrations, taken immediately pre-glucagon, and thereafter every 15 minutes for 60 minutes. A rise in glucose concentration of >1 mmol/l (55 infants) was defined as an adequate response to glucagon. An inadequate glycaemic response was <1 mmol/l (23 infants). RESULTS: Several differences in fasting blood glucose and hormone concentrations were identified in infants with an inadequate glycaemic response to glucagon compared to those with an adequate response: relative fasting hyperglycaemia (mean 3.7 v 3.3 mmol/l, p = 0.008); fasting hyperinsulinaemia (mean 4.3 v 2.6 mU/l, p = 0.014); an increased insulin:glucagon ratio (0.19 v 0.11, p = 0.014), and a lower insulin sensitivity QUICKI index (0.19 v 0.22, p = 0.04). There was no distinctive phenotype to reliably predict response to glucagon. CONCLUSION: Some preterm infants show an inadequate glycaemic response to glucagon and have features suggestive of insulin resistance. The potential long term implications of such insulin resistance may have appreciable public health consequences.
Blood Glucose↗
Polymorphisms in genes involved in glucose metabolism in cases of sudden infant death syndrome.
BACKGROUND: Infants with intra-uterine growth retardation have an increased risk of Sudden Infant Death Syndrome (SIDS). Hypoglycaemia is also significantly correlated with retardation of intra-uterine growth. A number of mutations in key proteins involved in regulation of blood glucose (e.g. glucokinase) have been found to result in reduced birth weight. Heterozygous mutations in the coding region of the glucokinase gene have been shown to cause MODY (a form of early onset Type II diabetes mellitus). The aim was to screen a cohort of SIDS and control infants who were either growth retarded or appropriately grown for gestational age to determine if any mutations and/or polymorphisms were present in the glucokinase gene. METHODS: PCR, denaturing high performance liquid chromatography on an automated Transgenomic WAVE DNA fragment analysis system and DNA sequencing. RESULTS: Genomic DNA was isolated from 129 infants who were either growth retarded or appropriately grown for gestational age. We found several rare novel polymorphisms in the glucokinase gene in the infant samples. However, none of the samples contained any of the mutations in the glucokinase gene previously reported in cases of MODY. CONCLUSIONS: We have found rare novel polymorphisms in the glucokinase gene in the infant samples. In contrast in these samples, we have not found any examples of the previously reported mutations in the coding region of the glucokinase gene found in MODY. This clearly shows that while MODY babies are often small, MODY is not a common cause of either intra-uterine growth retardation or of SIDS.
Chromatography, High Pressure Liquid↗
Developmental disorders of glucose metabolism in infants.
BACKGROUND: Developmental failures to adequately control postnatal blood glucose levels are common in the transition from fetal to infant life and can persist for many months. The standard method of functionally measuring hepatic glucose production and/or disordered glucose production is the response to a glucagon tolerance test. METHOD: We adapted the standard glucagon tolerance test used for children and adults for use in preterm infants. 79 consecutive preterm infants gestational age range 25-36 weeks (mean 32.2 weeks), mean birth weight 1.66 kg admitted to the Neonatal Intensive Care Unit, Ninewells Hospital, Dundee and who survived to discharge home were recruited into the study. At the time of discharge home the characteristics of the group were as follows: adjusted mean gestational age 36.7 weeks, mean discharge weight 2.23 kg. RESULTS: In this study of preterm infants the maximal increase in plasma glucose following administration of a glucagon tolerance test is 1.39 +/- 07 mmol/L, n = 78 (range 0-3.98 mmol/L). CONCLUSIONS: An increase in plasma glucose of less than 4 mmol/L is considered abnormal in adults following administration of a fasting glucagon tolerance test. The responses of preterm infants and adults to glucagon are clearly different. The attenuated response to glucagon in the preterm infants is consistent with the low levels of hepatic glucose-6-phosphatase activity in premature infants as glucose-6-phosphatase is the terminal step of the two main pathways of liver glucose production.
Blood Glucose↗
Thioredoxin reductase and cytoplasmic glutathione peroxidase activity in human foetal and neonatal liver.
Cytosolic thioredoxin reductase (TR) is an FAD-containing homodimeric selenoenzyme which, together with thioredoxin (Trx) and NADPH, forms a powerful oxidoreductase system. Cytoplasmic glutathione peroxidase (GPX-1) is a selenoprotein with antioxidant activity. The TR/Trx system has been associated with cellular processes including regulation of cell growth, and modification of activity of transcription factors. TR may also act as an antioxidant. We have measured TR activity, TR concentration, and GPX-1 activity in human hepatic cytosols from foetuses and neonates. The concentration of TR was significantly greater (P<0.05) in foetal (43.6, 37.9-50.8 microg/g protein, median, interquartile range) than in neonatal liver (11.6, 8.70-15.0 microg/g). This was also true of TR activity which was 2.1, 1.8-2.5 U/g protein in foetal, and 0.65, 0.44-0.74 U/g protein in neonatal liver (P<0.0005). Similarly, GPX-1 activity was significantly higher (P<0.005) in the foetal (199.7, 144.0-227.9 U/g protein) than in neonatal (77.0, 58.4-110.3 U/g protein) hepatic cytosol. Overall, foetal liver expressed approx. 3-fold higher activities of TR and GPX-1 than neonatal liver.
Autopsy↗
Deciding on treatment limitation for neonates: the parents' perspective.
UNLABELLED: The reported study aimed to explore parents' perceptions of treatment withdrawal/withholding; their experience and their opinions. In-depth face-to-face interviews at 3 and 13 months after the baby's death were conducted with 108 parents of 62 babies from the East of Scotland. Of the parents, 56% (60/180) believed they had decided to stop treatment. A further 4/59 sets of parents subsequently wished they had taken responsibility. Only one parent who did decide felt guilt 3 months after the event. Parents identified two essential factors which minimise doubt: full and honest information and concrete evidence of a poor prognosis. CONCLUSION: The majority of parents wish to be active in decision making on behalf of their baby. Doing so does not appear to have adverse consequences. The pacing of events in the process of deciding and managing the dying is critical. Dissatisfaction is reduced if parents are given time and evidence to help them assimilate the reality at each stage.
Adult↗
Regulation of prostaglandin availability in human fetal lung by differential localisation of prostaglandin H synthase-1 and prostaglandin dehydrogenase.
Specialisation of the respiratory portion of human fetal lung commences around 20-24 weeks gestation. In contrast, human fetal lung in vitro has the capacity to self-differentiate from 12 weeks gestation when grown in media devoid of growth factors or hormones, suggesting activation of autocrine or paracrine factors in vitro, or removal of the fetus from in utero inhibitory mechanisms. Prostaglandins play a key role during in vitro human fetal lung development and are synthesised by prostaglandin H synthase-1 (PGHS-1) and inactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH) with formation of inactive 13,14-dihydro-15-keto-prostaglandins. We have used quantitative immunohistochemistry to determine expression and localisation of PGHS-1, PGDH, PGE2 and 13,14-dihydro-15-keto-PGE2 (PGEM) in human fetal lung with in situ hybridisation to localise PGHS-1 and PGDH mRNA. For the catabolic enzyme PGDH, amounts of mRNA, protein and enzyme product PGEM are increased within epithelium of distal as compared to more proximal airways. For PGHS-1, comparable amounts of mRNA, protein and enzyme product PGE2 are found in proximal and distal lung epithelium. Catabolism by PGDH is a sensitive mechanism for regulating bioavailability of prostaglandins and we propose that active catabolism of prostaglandins within human fetal lung epithelium is an inhibitory mechanism retarding epithelial differentiation in utero.
Cyclooxygenase 1↗
Ketoacidosis: an unusual presentation of MELAS.
Explore the source record for details and available documents.
Blood Glucose↗
Transient hypothyroxinaemia in preterm infants.
Explore the source record for details and available documents.
Brain↗
Consent to autopsy for neonates.
OBJECTIVES: To determine parents' views on autopsy after treatment withdrawal. DESIGN: Face to face interviews with 59 sets of bereaved parents (108 individual parents) for whose 62 babies there had been discussion of treatment withdrawal. RESULTS: All except one couple were asked for permission for postmortem examination; 38% refused. The main reasons for declining were concerns about disfigurement, a wish to have the child left in peace, and a feeling that an autopsy was unnecessary because the parents had no unanswered questions. The diagnosis, the age of the child, and the approach of the consultant appeared to influence consent rates. Of those who agreed to autopsies, 92% were given the results by the neonatologist concerned. Whether or not they had agreed to the procedure, at 13 months no parent expressed regrets about their decision. CONCLUSIONS: Autopsy rates in the East of Scotland stand at 62%. Parents' perceptions are an important element in consent to postmortem examination.
Adolescent↗
Thyroid hormone metabolism and the developing human lung.
Thyroid hormones are involved in the regulation of fetal lung development, and maturation is accelerated in animal models by antepartum exposure to raised concentrations of the receptor-active thyroid hormone triiodothyronine and glucocorticoids. It is essential that the nature of the regulation of the spatial and temporal metabolism of iodothyronines in the human fetus and infant is known before effective therapies can be developed to modify human lung maturation. Thyroid hormone bioavailability to the human fetus is regulated in part by enzymatic deiodination and reversible sulfation of iodothyronines, with contributions from other factors such as fetomaternal and fetoamniotic hormone transfers, fetal thyroid gland production, and the activities of plasma membrane transporters mediating uptake of iodothyronines from plasma into tissues.
Arylsulfatases↗
Differential expression of sulfotransferase enzymes involved in thyroid hormone metabolism during human placental development.
Thyroid hormone is essential for normal human development, and disruption of thyroid hormone homeostasis at critical developmental stages can result in severe and often long-term effects on crucial organs such as the brain and lungs. Numerous factors control the bioavailability of receptor active thyroid hormone T(3). Sulfation, catalyzed by sulfotransferase enzymes (SULTs), is an important pathway of thyroid hormone metabolism by which T(4) is irreversibly converted to inactive reverse T(3) rather than active T(3). The human fetus and neonate have high levels of circulating sulfated iodothyronines, although the source of these is not clear. The placenta forms the link between the fetus and its mother and is involved in transfer of thyroid hormone early in pregnancy, although its capacity for sulfation is unknown. We therefore examined expression of the SULTs involved in iodothyronine metabolism during human placental development. SULT activity was measured in human placental cotyledon and membranes (amnion, chorion, and decidua basalis) from 13-42 wk of gestation, and Western blot analysis was employed to verify enzyme activity data. Phenol and catecholamine sulfotransferases were expressed at the highest levels and were generally higher in the villous than membranous tissues. SULT1A1 activity showed significant correlation with sulfation of 3,3'-T(2), suggesting that this enzyme is primarily responsible for placental T(2) sulfation. Estrogen sulfotransferase was present at extremely low levels during early pregnancy, although in mid- and late gestation increased expression in the (predominantly maternal-derived) decidual component of the placenta was observed. Hydroxysteroid sulfotransferase, T(3), reverse T(3), and T(4) SULT activities were also low in all tissues examined, and expression of SULTs 1B1 and 1C2 were essentially undetectable by Western blot analysis. The results highlight a tissue-specific regulation of SULT expression during placental development, demonstrate very low sulfation of iodothyronines suggesting that the placenta is not a major source of circulating sulfated iodothyronines in the fetus.
Female↗
Sulfation of thyroid hormone and dopamine during human development: ontogeny of phenol sulfotransferases and arylsulfatase in liver, lung, and brain.
Sulfation is an important mechanism for regulating the biological activity of numerous hormones and neurotransmitters in man. Here we have investigated the ontogeny of sulfotransferases (SULT) and sulfatase (ARS) involved in the metabolism of thyroid hormone and dopamine. SULT1A1 enzyme activity was lower in postnatal liver and lung than in fetal tissues. Hepatic SULT1A3 (dopamine) was expressed at high levels early in development, but decreased substantially in late fetal/early neonatal liver and was essentially absent from the adult liver. In lung, significant SULT1A3 activity was observed in the fetus, but neonatal levels were considerably lower. In brain, the highest activity was observed in the choroid plexus for SULT1A1, with low and widespread activity for both SULT1A1 and SULT1A3 in other brain regions. SULT activity with 3,3'-diiodothyronine (3,3'-T(2)) as substrate was measured in all tissues and correlated significantly with SULT1A1 activity (4-nitrophenol), suggesting that SULT1A1 is primarily responsible for the sulfation of this iodothyronine. The developmental expression of SULT1A3 and SULT1A1 in liver and brain was confirmed by immunoblot, and immunohistochemistry of developing liver showed substantial expression of these proteins in hemopoietic cells in fetal liver. We also detected low activity for the hydrolysis of 3,3'-T(2) sulfate by ARS, although there was less distinction between fetal and neonatal samples than with SULT activities. We have therefore shown that the developing fetus has substantial sulfation capacity. Sulfation may therefore play a major role in the homeostasis of hormones and other endogenous compounds as well as in detoxification in the fetus, particularly as other conjugating enzyme systems, such as the UDP-glucuronosyltransferases, are not expressed at significant levels until the neonatal period.
Aging↗
Factors affecting fetal weight distribution in women with type I diabetes.
OBJECTIVE: To identify factors independently affecting fetal weight in women with type I diabetes. DESIGN: Prospectively recorded data in consecutive women with type I diabetes, between 1975-1992. SETTING: Simpson Memorial Maternity Hospital, Edinburgh. Population Three hundred and two pregnancies with type I diabetes identified before pregnancy, with antenatal care and delivery in the Simpson Memorial Maternity Hospital, a singleton pregnancy, and the same diabetic physician. METHODS: Normal ranges for birthweight were established for the total hospital population. All cases and the total population had pregnancy dating by ultrasound. The relation between standardised birthweight and explanatory variables was investigated using correlation analysis, t tests and chi2 tests as appropriate, and subsequently using multiple linear regression. RESULTS: Standardised birthweight in cases, compared with the reference population, showed a unimodal, approximately normal distribution, markedly shifted to the right (mean + 1.26 SD). The most predictive variable was glycated haemoglobin concentration at 27-33 weeks, which explained 6.3% of the birthweight variance, while smoking explained 2.7% and maternal weight 2.0%. There was a trend towards a negative relationship with glycated haemoglobin concentration at 6-12 weeks. Smoking and glycated haemoglobin concentration were strongly intercorrelated. CONCLUSIONS: Most of the variance in standardised birthweight remains unexplained, but glycated haemoglobin concentration at 27-33 weeks is the most powerful explanatory variable. Possible reasons why there is not a stronger relationship between markers of maternal glycaemia and birthweight are discussed.
Birth Weight↗
Therapeutic insulin and hepatic glucose-6-phosphatase activity in preterm infants.
BACKGROUND: Hepatic glucose-6-phosphatase activity is low at birth, and in term infants rises rapidly to adult levels. In contrast, in most preterm infants, it remains low postnatally making them vulnerable to repeated hypoglycaemic episodes, resultant cerebral damage, or risk of sudden and unexpected death. AIMS: To investigate the clinical features of preterm infants with low glucose-6-phosphatase enzyme activity to determine the influencing factors. METHODS: Clinical data from 36 preterm infants were correlated by stepwise multiple regression analysis with V(max) of hepatic glucose-6-phosphatase as the dependent variable. RESULTS: The most significant correlation was with the administration of insulin (units/kg/h postnatal life) with lesser effects of respiratory distress syndrome and dopamine administration. The V(max) changes reflected changes in the level of expression of the glucose-6-phosphatase protein. CONCLUSION: In a variety of animal models, hepatic glucose-6-phosphatase levels have been shown to decrease in response to insulin, which also decreases transcription of the glucose-6-phosphatase gene. The association of insulin administration with high levels of hepatic glucose-6-phosphatase activity and protein expression was therefore most unexpected. Results from model systems, or adults, must be extrapolated to the metabolism of preterm infants with caution.
Blood Glucose↗
Focused obstetrical clinic for active duty junior enlisted service women: model for improved outcomes.
OBJECTIVE: To evaluate the utility of an interdisciplinary clinic in improving perinatal outcomes for all pregnant patients of junior enlisted rank (E4 and below) in response to previous reports that this group is at higher risk for adverse outcomes. METHODS: The study population included all junior enlisted active duty patients (E4 and below) delivering between January 1, 1993, and June 30, 1996. Outcomes for patients receiving care in a focused active duty obstetrical clinic were compared with outcomes in similar cohorts of senior active duty patients (E5 and above) and non-active duty pregnant patients. Evaluation was based on perinatal outcomes, including chorioamnionitis, postpartum hemorrhage, intrauterine growth retardation, cesarean delivery, preterm delivery rates (< 37 weeks), postterm delivery rates (> 41 weeks), postpartum days, mean gestational age at delivery, mean delivery weights, Apgar scores at 1 and 5 minutes, preeclampsia, and premature labor. Variables with potential to confound perinatal outcomes were also studied. Confounding variables included tobacco use, gestational diabetes, chronic hypertension, thyroid disease, history of substance abuse, and alcohol use. Power analysis accomplished before initiation of the study showed adequate sample size (> 240 patients in each group) to demonstrate statistically different rates of preterm delivery. Statistical analysis was done using the chi 2 test for categorical variables and Student's t test for continuous variables. RESULTS: There were no statistical differences between junior active duty patients, senior active duty patients, and non-active duty patients in preterm delivery and other outcome variables. CONCLUSION: The focused obstetrical clinic, conducted for junior enlisted soldiers by a senior nurse practitioner, appears to provide an intervention that ensures perinatal outcomes equal to those of both the non-active duty and the senior active duty population.
Adult↗
Regulation of thyroid hormone metabolism during fetal development.
Compared with adults, plasma T3 concentrations in the human fetus are decreased, whereas levels of rT3 and the different iodothyronine sulfates, T4S, T3S, rT3S and 3,3'-T2S, are increased. The low T3 and high rT3 concentrations reflect the preponderance of inner ring versus outer ring deiodinase activity due to high type III iodothyronine deiodinase (D3) expression in fetal tissues, such as liver and brain, the placenta, and perhaps also the uterus, in combination with still incomplete expression of hepatic type I iodothyronine deiodinase (D1) expression. In contrast to humans, D3 is hardly expressed in the fetal rat liver. However, high D3 expression is observed in the embryonic chicken liver which decreases dramatically towards the end of incubation, resulting in a marked increase in plasma T3. Thyroid hormone is essential for the development of the brain, in which local conversion of the prohormone T4 to the active hormone T3 by the type II iodothyronine deiodinase (D2) plays a very important role. In contrast to the rat, however, little is known about the ontogeny of D2 in different human brain areas. The cause of the high concentrations of sulfated iodothyronines in fetal plasma is unknown. In adults, the liver is an important site for the clearance of these conjugates, where they are rapidly degraded by D1. Although fetal human liver expresses significant D1 activity, clearance of iodothyronine sulfates may be defective due to the lack of transporters mediating their hepatic uptake. However, production of iodothyronine sulfates may also be increased in the human fetus, although the responsible sulfotransferases and their location remain to be identified. Sulfation may be a reversible pathway of thyroid hormone inactivation, depending on the recovery of free hormone by sulfatases. However, little is known at present about the characteristics and regulation of these enzymes in fetal human tissues. Further studies are required to increase our understanding of the tissue-specific and stage-dependent regulation of thyroid hormone bioactivity during human development.
Animals↗